What causes hypertension?

Causes of High Blood Pressure (Hypertension)

High blood pressure is primarily caused by a complex interaction of genetic predisposition and environmental factors, with obesity, excess sodium intake, physical inactivity, and alcohol consumption being the most significant modifiable contributors. 1

Genetic Factors

• Hypertension is a complex polygenic disorder where many genes or gene combinations influence blood pressure 1
• While several rare monogenic forms of hypertension exist (e.g., glucocorticoid-remediable aldosteronism, Liddle's syndrome, Gordon's syndrome), these account for only a small percentage of cases 1
• More than 25 rare mutations and 120 single-nucleotide polymorphisms have been identified as contributing to blood pressure regulation 1
• The collective effect of all blood pressure loci identified through genome-wide association studies accounts for only about 3.5% of blood pressure variability 1
• Individuals with a high number of small-effect alleles associated with higher blood pressure tend to experience more rapid increases in blood pressure with age 1

Environmental and Lifestyle Factors

Obesity and Overweight

• Direct relationship between body mass index and blood pressure that is continuous and almost linear 1
• Central obesity (measured by waist-to-hip ratio or CT scans) shows an even stronger relationship with blood pressure than general obesity 1
• Attributable risk estimates suggest obesity may be responsible for 40-78% of hypertension cases 1
• Being continuously obese or acquiring obesity is associated with a 2.7-fold increased risk of developing hypertension 1
• Weight loss can reduce the risk of hypertension to levels similar to those who were never obese 1

Sodium Intake

• Sodium intake is positively associated with blood pressure in multiple study types (migrant, cross-sectional, prospective cohort) 1
• Excessive sodium consumption accounts for much of the age-related increase in blood pressure 1
• Beyond its effect on blood pressure, high sodium intake is independently associated with increased risk of stroke, cardiovascular disease, and other adverse outcomes 1
• Certain populations are particularly salt-sensitive, including Black individuals, older adults, and those with comorbidities such as chronic kidney disease, diabetes, or metabolic syndrome 1

Dietary Factors

• Insufficient intake of potassium, calcium, magnesium, protein (especially from vegetables), fiber, and fish fats are associated with higher blood pressure 1
• Poor diet is an underlying cause of a large proportion of hypertension cases 1
• Gut microbiota has also been linked to hypertension, especially in experimental animals 1

Physical Inactivity

• Sedentary lifestyle is strongly associated with development of hypertension 2
• Regular physical activity can delay the development of hypertension and reduce blood pressure in those already diagnosed 2
• Both aerobic and resistance exercise effectively reduce blood pressure 2

Alcohol Consumption

• Excessive alcohol intake contributes to elevated blood pressure 1
• Reducing alcohol consumption can significantly lower systolic and diastolic blood pressure, particularly in those consuming 3 or more drinks per day 1

Psychosocial Factors

• Chronic stress and occupational stress (job strain) have been associated with higher blood pressure 3
• Social factors such as urbanization and education level are related to hypertension prevalence 3

Pathophysiological Mechanisms

• Hypertension involves complex interactions between environmental factors, genes, hormonal networks, and multiple organ systems (renal, cardiovascular, and central nervous) 1
• Vascular and immune mechanisms play important roles in the development of hypertension 1
• Overactivity of the sympathetic nervous system is implicated in the development of hypertension, particularly in its early stages 3
• Endothelial dysfunction, altered vasoreactivity, vascular remodeling, fibrosis, inflammation, and increased peripheral vascular resistance contribute to the pathophysiology 1

Secondary Hypertension

• Approximately 10% of hypertension cases have an identifiable cause (secondary hypertension) 1
• Common causes of secondary hypertension include:
  • Renal parenchymal disease (chronic glomerulonephritis, polycystic kidney disease) 1
  • Renovascular disease 1
  • Endocrine disorders (primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperparathyroidism, thyroid disorders) 1
  • Obstructive sleep apnea 1
  • Medication or substance use (NSAIDs, cocaine, amphetamines) 1
  • Coarctation of the aorta 1

Clinical Implications

• Understanding the causes of hypertension is crucial for effective prevention and management strategies 4
• First-line therapy for hypertension includes lifestyle modifications targeting the modifiable risk factors: weight loss, dietary sodium reduction, increased potassium intake, physical activity, and limited alcohol consumption 4
• When pharmacological treatment is needed, thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers are recommended as first-line therapies 5, 6, 4
• Controlling high blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions 5, 6

Common Pitfalls in Addressing Hypertension Causes

• Focusing solely on pharmacological treatment without addressing underlying modifiable risk factors 4
• Failing to consider the possibility of secondary hypertension, especially in patients with resistant hypertension or sudden onset of hypertension 1
• Not recognizing the cumulative and interactive effects of multiple risk factors 3
• Overlooking the importance of long-term lifestyle modifications in addition to medication 4
• Underestimating the contribution of genetic factors, which may influence response to both lifestyle interventions and medications 7, 8